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Moreover, the biological effects of nanometer\u2010size chromium oxide particles, the predominant type of wear particles produced by MM implants, remain mostly unknown. The purpose of this study was to analyze the cytotoxic effects of clinically relevant nanometer\u2010size chromium oxide particles on macrophage response <jats:italic>in vitro<\/jats:italic>. J774.A1 macrophages were cultured with either 60 nm or 700 nm commercially available Cr<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> particles at different concentrations. Two different particle sizes were analyzed to evaluate potential volume effects. Cell mortality was analyzed by light microscopy, flow cytometry (annexin V\u2010fluorescein isothiocyanate and propidium iodide assay), and using a cell death detection enzyme\u2010linked immunosorbant assay (ELISA). Tumor necrosis factor alpha (TNF\u2010\u03b1), monocyte chemotactic protein\u20101 (MCP\u20101), and macrophage inflammatory protein\u20101 alpha (MIP\u20101\u03b1) release was measured by ELISA, and gene expression was analyzed by quantitative real\u2010time PCR. Results showed that, at high concentrations, Cr<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> particles of both sizes can be cytotoxic, inducing significant decreases in total cell numbers and increases in necrosis. Results also suggested that these effects were dependent on particle volume. However, TNF\u2010\u03b1, MCP\u20101, and MIP\u20101\u03b1 cytokine release and gene expression remained low. Overall, this study demonstrates that nanometer\u2010size particles of Cr<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>, a stable form of chromium oxide ceramic, have rather low cytotoxic effects on macrophages. Therefore, these particles may not be the main culprit in the initiation of the inflammatory reaction in MM periprosthetic tissues. However, other parameters (e.g., potential intracellular damage) remain to be investigated. \u00a9 2013 Wiley Periodicals, Inc. 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